Intestinal bacterial microflora—a potential source of chronic inflammation in patients with chronic kidney disease

Kotanko, Peter; Carter, Mary; Levin, Nathan W.

doi:10.1093/ndt/gfl281

Cited by 74 publications

(55 citation statements)

References 27 publications

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“…HD itself appears to be responsible for increasing exposure to translocated intestinal endotoxin, as evidenced by a large difference between patients with very severe CKD stage 5 but not yet started on dialysis and those receiving dialysis. Predialysis CKD stage 5 patients are very similar for demographic factors and comorbidities when compared to patients established on HD.…”

Section: Discussionmentioning

confidence: 99%

“…Endotoxin is released by bacterial cell wall breakdown within and beyond the gut lumen, from effective host defense mechanisms and by autolysis. Endotoxin enters the circulation via bacterial translocation (passage of intact bacteria and macromolecules such as endotoxin across the intestinal barrier [5]), with bowel edema and hypoperfusion being the two main factors influencing bowel wall permeability in congestive heart failure (6). Dialysis patients are characteristically volume overloaded.…”

Section: Introductionmentioning

confidence: 99%

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Circulating Endotoxemia

McIntyre

Harrison

Eldehni

et al. 2011

Clinical Journal of the American Society of Nephrology

400

406

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SummaryBackground and objectives Translocated endotoxin derived from intestinal bacteria has a wide range of adverse effects on cardiovascular (CV) structure and function, driving systemic inflammation, atherosclerosis and oxidative stress. This study's aim was to investigate endotoxemia across the spectrum of chronic kidney disease (CKD).Design, setting, participants, & measurements Circulating endotoxin was measured in 249 patients comprising CKD stage 3 to 5 and a comparator cohort of hypertensive patients without significant renal impairment. Patients underwent extended CV assessment, including pulse wave velocity and vascular calcification. Hemodialysis (HD) patients also received detailed echocardiographic-based intradialytic assessments. Patients were followed up for 1 year to assess survival. ResultsCirculating endotoxemia was most notable in those with the highest CV disease burden (increasing with CKD stage), and a sharp increase was observed after initiation of HD. In HD patients, predialysis endotoxin correlated with dialysis-induced hemodynamic stress (ultrafiltration volume, relative hypotension), myocardial stunning, serum cardiac troponin T, and high-sensitivity C-reactive protein. Endotoxemia was associated with risk of mortality.Conclusions CKD patients are characteristically exposed to significant endotoxemia. In particular, HD-induced systemic circulatory stress and recurrent regional ischemia may lead to increased endotoxin translocation from the gut. Resultant endotoxemia is associated with systemic inflammation, markers of malnutrition, cardiac injury, and reduced survival. This represents a crucial missing link in understanding the pathophysiology of the grossly elevated CV disease risk in CKD patients, highlighting the potential toxicity of conventional HD and providing a novel set of potential therapeutic strategies to reduce CV mortality in CKD patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Circulating Endotoxemia

McIntyre

Harrison

Eldehni

et al. 2011

Clinical Journal of the American Society of Nephrology

400

406

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“…Hida et al studied the fecal flora of hemodialysis (HD) patients and healthy controls using traditional plating methods and found quantitative and qualitative differences between the two groups (13). It is plausible to suggest that the chronic inflammatory state in dialysis patients is in part due to a microbial imbalance in the gut, resulting in alteration of proinflammatory cytokines and production of uremic toxins from proteins fermented in the large intestine (16). Moreover, impaired intestinal barrier function in peritoneal dialysis (PD) patients allows enteric organisms to enter the peritoneal cavity by transmural migration and to cause peritonitis (8,27).…”

mentioning

confidence: 99%

Real-Time PCR Analysis of the Intestinal Microbiotas in Peritoneal Dialysis Patients

Wang

Lai

et al. 2012

Appl Environ Microbiol

106

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Bifidobacterium and Lactobacillus can beneficially affect the host by producing acetic acid and lactic acid, which lower pH and thereby inhibit the growth of pathogens or allow the probiotic bacteria to compete with pathogens for epithelial adhesion sites and nutrients. The transmural migration of enteric organisms into the peritoneal cavity can cause peritonitis in peritoneal dialysis (PD) patients. We hypothesized that the composition of the intestinal microbiota with regard to Lactobacillus species and Bifidobacterium species differed between PD patients and healthy controls. The aim of the study was to investigate these differences by real-time PCR analysis of fecal samples. There is a large, complex, and diverse microbial community in the human intestine. The intestinal microbiota plays an important role in digesting food, metabolizing endogenous and exogenous compounds, and producing essential vitamins. It also stimulates the immune system and prevents the colonization of the gastrointestinal tract by pathogens, and hence it influences human health (7, 9). The gastrointestinal microbiota of an adult human consists of more than 500 species, with 10 11 to 10 12 CFU per gram of stool (12,25). The predominant microorganisms are non-spore-forming, obligate anaerobes, such as Bacteroides, Fusobacterium, Eubacterium, and Bifidobacterium species. Other anaerobic bacteria found in large numbers include Lactobacillus species, various anaerobic Gram-positive cocci, and Clostridium species (4). Hida et al. studied the fecal flora of hemodialysis (HD) patients and healthy controls using traditional plating methods and found quantitative and qualitative differences between the two groups (13). It is plausible to suggest that the chronic inflammatory state in dialysis patients is in part due to a microbial imbalance in the gut, resulting in alteration of proinflammatory cytokines and production of uremic toxins from proteins fermented in the large intestine (16). Moreover, impaired intestinal barrier function in peritoneal dialysis (PD) patients allows enteric organisms to enter the peritoneal cavity by transmural migration and to cause peritonitis (8,27). Peritonitis occasionally causes death and results in significant morbidity, including catheter loss, transfer to hemodialysis, transient loss of ultrafiltration, and possible permanent membrane damage (22). Bifidobacterium and Lactobacillus can beneficially affect the host by inhibiting the growth of pathogens through production of acetic acid and lactic acid, which lower pH, or by competing with pathogens for epithelial adhesion sites and nutrients (10).To the best of our knowledge, no study has investigated the intestinal microbiota in PD patients before. The aim of this study, therefore, was to evaluate the differences in the intestinal microbiota between PD patients and healthy controls by examining fecal samples. We focused on Bifidobacterium species, Lactobacillus species, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterococcus species....

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“…In chronic kidney disease patients, endotoxin enters the circulation via bacterial translocation (the passage of intact bacteria and macromolecules such as endotoxin across the intestinal barrier) (Kotanko et al 2006). In congestive heart failure, bowel edema and hypoperfusion may be the two main factors influencing bowel wall permeability (Krack et al 2005).…”

Section: Discussionmentioning

confidence: 99%